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Lysophosphatidic acid regulates inflammation-related genes in human endothelial cells through LPA1 and LPA3 |
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| Authors: | Lin Chi-Iou Chen Chiung-Nien Lin Po-Wei Chang King-Jen Hsieh Fong-Jou Lee Hsinyu |
| Affiliation: | a Institute of Zoology, National Taiwan University, Taipei 106, Taiwan, ROC b Department of Life Science, National Taiwan University, Taipei 106, Taiwan, ROC c Angiogenesis Research Center, National Taiwan University, Taipei 106, Taiwan, ROC d Department of Surgery, National Taiwan University Hospital, Taipei 106, Taiwan, ROC e Department of Medical Ultrasound, National Taiwan University Hospital, Taipei 106, Taiwan, ROC f Division of Mechanics, Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan, ROC |
| Abstract: | Lysophosphatidic acid (LPA) is a low-molecular-weight lysophospholipid (LPL), which regulates endothelial cells participating in inflammation processes via interactions with endothelial differentiation gene (Edg) family G protein-coupled receptors. In this study, we attempted to determine which LPA receptors mediate the inflammatory response in human endothelial cells. Introduction of siRNA against LPA1 significantly suppressed LPA-induced ICAM-1 mRNA, total protein, and cell surface expressions, and subsequent U937 monocyte adhesion to LPA-treated human umbilical endothelial cells (HUVECs). By knock down of LPA1 and LPA3 in HUVECs, LPA-enhanced IL-1β mRNA expression was significantly attenuated. Moreover, LPA1 and LPA3 siRNA also inhibited LPA-enhanced IL-1-dependent long-term IL-8 and MCP-1 mRNA expression, and subsequent THP-1 cell chemotaxis toward LPA-treated HUVEC-conditioned media. These results suggest that the expression of LPA-induced inflammatory response genes is mediated by LPA1 and LPA3. Our findings suggest the possible utilization of LPA1 or LPA3 as drug targets to treat severe inflammation. |
| Keywords: | LPA LPA1 LPA3 Endothelial cells |
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